INJURY STIMULATES OUTGROWTH AND MOTILITY OF OLIGODENDROCYTES GROWN IN-VITRO

Oligodendrocytes which form myelin within the CNS develop from small, highly motile cells that are largely bipolar into mature cells which e xtend many processes and which produce myelin membranes around multipl e axons. The production of myelin sheaths is thought to anchor mature oligodendrocytes (OLs), limiting their motility. When the brain sustai ns an injury, OLs do not make a significant effort to remyelinate, a f act attributed to both their lack of proliferation and their inability to migrate or extend processes into areas of injury. To test the moti lity and growth potential of mature OLs, we have designed an in vitro system in which individual cells can undergo longterm observation. Add itionally, cells can be mechanically injured by transection of process es using a low-power laser beam. Both control and injured OLs undergo several types of structural change, including extension and retraction of processes and membranes, as well as changes in process caliber. So me OLs exhibit a high degree of motility, moving several hundred micro meters within days. Rather than interfering with the cells' ability to undergo structural change, injury actually stimulated outgrowth of ne w processes and motility. Neither injury nor addition of basic fibrobl ast growth factor (bFGF) increased the rate of OL division. However, b FGF paradoxically caused an increase in uptake of the DNA synthesis ma rker bromodeoxyuridine and had negative effects on OL survival. The un expected findings that OLs with a mature phenotype are motile and unde rgo constant structural modification in vitro and that injury induces certain behaviors suggest that myelin-forming OLs in the brain may be capable of a high degree of plasticity under certain conditions. (C) 1 997 Academic Press.